This application is related to U.S. Pat. No. 8,044,033, issued Oct. 25, 2011, the entirety of which is incorporated herein by reference.
1. Field of the Invention
The present invention relates generally to the field of molecular biology and oncology. More particularly, it concerns methods for detecting cancer stem cells and for determining a response to anti-cancer therapy.
2. Description of Related Art
Colorectal cancer is the second most common cause of cancer-related death in the United States (Jemal et al., 2005). The benchmark median overall survival of patients receiving first-line and second-line combination chemotherapy for metastatic colorectal cancer is currently 17-20 months and 10-12 months, respectively (Douillard et al., 2000; Goldberg et al., 2004; Tournigand et al., 2004; Rothenberg et al., 2003; Hurwitz et al., 2004; Giantonio et al., 2005; Cunningham et al., 2004; Diaz Rubio et al., 2005). Unfortunately, the five year overall survival was merely 5-8%.
Various combination therapies have been used to address this form of cancer. Combining bevacizumab or cetuximab with cytotoxic chemotherapy produced response rate to 60-80%, converting more patients to be surgically resectable, but not overall complete response (CR) rate ranging between 2-10% (Hurwitz et al., 2004; Diaz Rubio et al., 2005; Hochster, 2006). However, little is known about natural history of the 2-10% CR patients from chemotherapy, as majority do relapse within two years. The natural history of these surgical CR patients may be the closest approximation to that of the CR patients rendered by chemotherapy.
In xenograft models, adding celecoxib (XCEL) (CELEBREX®; Pfizer, New York, N.Y.) a selective COX-2 inhibitor, to chemotherapy or radiation therapy significantly increased antitumor efficacy compared to either treatment modality alone (Cianchi et al., 2001; Masferrer et al., 2000; Sheng et al., 1998; Milas, 2003). More recently it was shown in a study of 66 patients with metastatic colorectal cancer who underwent XCEL (in combination with capecitabine)+/−radiation therapy experienced reduced toxicities and that nineteen (29%) of sixty-six patients unexpectedly achieved CR with XCEL alone (n=9) or with radiation (n=12), see e.g., U.S. Pat. No. 8,044,033. However, there remains no method to predict which patient have achieved CR following such therapy or to determine whether residual cancer stem cells remain in patients.